High Cut-Off Hemofiltration versus Standard Hemofiltration: A Pilot Assessment of Effects on Indices of Apoptosis

Abstract

Objectives: To measure plasma pro-apoptotic and pro-necrotic activity in severe acute kidney injury (AKI) patients within a randomized controlled trial of continuous veno-venous hemofiltration with high cut-off filters (CVVH-HCO) versus standard filters (CVVH-Std). Methods: We measured pro-apoptotic and pro-necrotic plasma activity by trypan blue exclusion cell viability assay, detection of DNA fragmentation, and by determination of caspase-3 activity and annexin V-based apoptosis and necrosis detection assay. Results: Compared to no apoptosis or necrosis after incubation with healthy plasma, 14-18% of cells showed apoptosis and 4-8% showed necrosis after incubation with plasma from AKI patients. When comparing different measures of pro-apoptotic or pro-necrotic activity, CVVH-HCO and CVVH-Std showed no differential effects on such activity, which remained high over the first 3 days of treatment. However, using annexin V-FITC, there was a significant drop in pro-apoptotic activity across the filter for the CVVH-HCO group (p = 0.043) but not for the CVVH-Std group (p = 0.327) and a significant difference between the two groups (CVVH-HCO vs. CVVH-Std p = 0.006). Conclusions: Patients with severe AKI have increased pro-apoptotic and pro-necrotic activity. Although on single-pass effect assessment, CVVH-HCO was superior to CVVH-Std in decreasing annexin V-FITC-assessed pro-apoptotic activity, there was no overall attenuation of such activity during the first 3 days of treatment.

Acute kidney injury in the ICU: from injury to recovery: reports from the 5th Paris International Conference

“…Recently, a randomized controlled trial (ClinicalTrials.gov Identifier: NCT00912184) completed recruitment of 76 patients with the aim to compare vasopressor requirements during HCO (100 kDa) CVVH or standard (30 kDa) CVVH. In a subset of patients enrolled in that trial, pro-apoptotic plasma activity was compared between the two groups [107]. At baseline, apoptotic activity in these AKI patients’ plasma was evident by DNA fragmentation, caspase-3 activity and phosphatidylserine exposure on cell membranes.…”

The Techniques of Blood Purification in the Treatment of Septic Shock

“…Moreover, despite the result of an experimental study showing a reduction of the catecholamine request in a porcine model of sepsis, a recent study of cascade HVHF in septic shock patients failed to demonstrate any beneficial effect when compared with standard care 14 . The of HCO membranes has been associated with the reduction of several septic mediators in some studies but other investigation did not confirm these findings 24,25 .…”

Blood Purification Techniques for Sepsis and Septic AKI

“…HCO membranes have shown promising properties on inflammation mediators removal, although the level of evidence is still low. When assessing the single-pass effect and compared to standard-CVVH, HCO-CVVH resulted in lowering one of the apoptosis indices in a pilot study of AKI patients (87). On the opposite, it did not modify nucleosome concentration of levels of TLR2 and TLR4 expression (88).…”